Inclusion Criteria:

- Pathologic or cytologic documentation of pancreatic adenocarcinoma

- Metastatic or locally advanced unresectable disease, including borderline
unresectable disease

- Patients with biliary or gastroduodenal obstruction must have drainage or surgical
bypass prior to starting chemoradiation

- Measurable or non-measurable assessable disease

- No prior treatment (chemotherapy, biological therapy, or radiotherapy) for
metastatic or non-metastatic locally advanced unresectable pancreatic cancer

- 6 months since completion of any prior neoadjuvant or adjuvant therapy (chemotherapy
or radiotherapy) for resected pancreatic cancer

- No prior treatment with oxaliplatin or irinotecan

- No prior treatment with fluoruouracil or capecitabine unless administered as a
radiosensitizing drug during adjuvant/neoadjuvant chemoradiotherapy after/before
resection of pancreatic cancer

- Patients who received chemotherapy > 2 years ago for malignancies other than
pancreatic cancer are eligible, provided that chemotherapy was completed > 2 years
ago and there is no evidence of the second malignancy at the time of study entry

- > 4 weeks since major surgery

- No other concurrent anticancer therapy

- ECOG Performance Status: 0-1

- Age > 18

- No other malignancy within past two years except basal cell carcinoma of the skin,
cervical carcinoma in situ, or nonmetastatic prostate cancer

- Paraffin block or slides must be available

- Adequate organ function

- No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the
lung

- No > grade 1 sensory peripheral neuropathy

- No uncontrolled seizure disorder, active neurological disease, or known CNS disease

- No significant cardiac disease, including the following: unstable angina, New York
Heart Association class II-IV congestive heart failure, myocardial infarction within
six months prior to study enrollment

- No history of chronic diarrhea

- Not pregnant and not nursing

- No other medical condition or reason that, in the opinion of the investigator, would
preclude study participation

- Laboratory parameters as follows: absolute neutrophil count ≥ 1,500/uL, platelet
count ≥ 100,000/uL, hemoglobin ≥ 9 g,/dL, creatinine < 1.5 X ULN or estimated GFR >
30 ml/min, bilirubin < 1.5 X ULN, AST and ALT < 3 X ULN, negative pregnancy test in
women of childbearing age